title: miR-302b maintains "stemness" of human embryonal carcinoma cells by post-transcriptional regulation of Cyclin D2 expression.
abstract: Embryonic stem cells (ESCs) and embryonal carcinoma cells (ECCs) possess the remarkable property of self-renewal and differentiation potency. They are model preparations for investigating the underlying mechanisms of "stemness". microRNAs are recently discovered small noncoding RNAs with a broad spectrum of functions, especially in control of development. Here, we show that miR-302b indirectly regulates expression of the pluripotent stem cell marker Oct4, and it directly regulates expression of Cyclin D2 protein, a developmental regulator during gastrulation. Using loss-of function and gain-of function approaches, we demonstrate that functional miR-302b is necessary to maintain stem cell self-renewal and inhibit neuronal differentiation of human ECCs. During retinoic acid-induced neuronal differentiation, Cyclin D2 protein but not mRNA expression is strongly increased, concurrent with the down-regulation of miR-302b and Oct4. Our results suggest that miR-302b plays an important role in maintaining the pluripotency of ECCs and probably ESCs, by post-transcriptional regulation of Cyclin D2 expression.
authors.affiliation: Division of Molecular Medicine, Beckman research Institute of the City of Hope, Duarte, CA, USA.
authors.forename: Nan Sook
authors.initials: NS
authors.lastname: Lee
authors.affiliation: Department of Anatomy and Cell Biology and Department of Biomedical Science, College of Medicine, Hanyang University, Seoul, Republic of Korea.
authors.forename: Jong Soo
authors.initials: JS
authors.lastname: Kim
authors.affiliation: Department of Anatomy and Cell Biology and Department of Biomedical Science, College of Medicine, Hanyang University, Seoul, Republic of Korea.
authors.forename: Wha Ja
authors.initials: WJ
authors.lastname: Cho
authors.affiliation: Department of Anatomy and Cell Biology and Department of Biomedical Science, College of Medicine, Hanyang University, Seoul, Republic of Korea.
authors.forename: Man Ryul
authors.initials: MR
authors.lastname: Lee
authors.affiliation: Department of Biology and Department of Diplomacy and World Affairs, Occidental College, CA, USA.
authors.forename: Riley
authors.initials: R
authors.lastname: Steiner
authors.affiliation: Department of Biological Sciences, Califonia State University, Los Angeles, CA, USA.
authors.forename: Andrea
authors.initials: A
authors.lastname: Gompers
authors.affiliation: Division of Neuroscience, Beckman research Institute of the City of Hope, Duarte, CA, USA.
authors.forename: Daijun
authors.initials: D
authors.lastname: Ling
authors.affiliation: Division of Neuroscience, Beckman research Institute of the City of Hope, Duarte, CA, USA.
authors.forename: Jae
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Pl
authors.initials: P
authors.lastname: Strom
authors.affiliation: Integrated DNA Technologies, Inc., Coralville, IA, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Behlke
authors.affiliation: CHA Stem Cell Institute & CHA Biotech, Pochon CHA University, Seoul, Republic of Korea.
authors.forename: Sung-Hwan
authors.initials: SH
authors.lastname: Moon
authors.affiliation: Division of Neuroscience, Beckman research Institute of the City of Hope, Duarte, CA, USA.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Salvaterra
authors.affiliation: Division of Molecular Medicine, Beckman research Institute of the City of Hope, Duarte, CA, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Jove
authors.affiliation: Department of Anatomy and Cell Biology and Department of Biomedical Science, College of Medicine, Hanyang University, Seoul, Republic of Korea. Electronic address: ks66kim@hanyang.ac.kr.
authors.forename: Kye-Seong
authors.initials: KS
authors.lastname: Kim
mesh_terms: D002454:Cell Differentiation; D045744:Cell Line, Tumor; D056742:Cyclin D2; D016213:Cyclins / Q000096:biosynthesis* / Q000235:genetics; D054278:Embryonal Carcinoma Stem Cells / Q000166:cytology / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D014176:Protein Biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D015533:Transcriptional Activation
chemical_list: C080336:CCND2 protein, human; D056742:Cyclin D2; D016213:Cyclins; C532169:MIRN302A microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger